KR20170128097A - Skin external agent for improving skin wrinkle comprising an extract of fermented wheat germ - Google Patents

Abstract

The present invention relates to an external application composition for preventing, alleviating, or treating skin wrinkles, wherein the external application composition comprises a compound of chemical formula 1, a fermented wheat germ, or an extract thereof as an active ingredient. The fermented wheat germ or the extract thereof includes the compound of the chemical formula 1. The fermented wheat germ is obtained by inoculating yeast to a wheat germ or a culture medium containing the same and by culturing the yeast. The yeast is Saccharomyces cerevisiae. The culturing is performed at 20 to 40C for 12 to 60 hours.

Description

[0001] The present invention relates to an external composition for improving skin wrinkles containing an extract of a fermented wheat germ extract as an active ingredient,

The present invention relates to a composition for external application for improving skin wrinkles containing an extract of a fermented wheat germ as an active ingredient.

In general, skin wrinkles are known to be produced by various factors such as moisture content of skin, collagen content, and immunity against external environment. Among the above, it is known that collagen has the greatest influence on the formation of wrinkles in the skin have.

Collagen is present mostly in the dermis of the skin and occupies about 70 ~ 80% of the dry weight of the skin, supporting the skin occupying most of the extracellular matrix. However, collagen biosynthesis is reduced by internal factors such as decrease of cell activity due to natural aging, accelerated degradation of collagen by external factors such as increase of stress due to harmful environment and sunlight, destruction of skin substrate As a result, wrinkles are generated. Therefore, a lot of research has been conducted on active ingredients that can prevent and improve such phenomena.

Elastase, which exists in the neutrophil granulocyte of human body, is an enzyme that decomposes elastin, a substrate protein important for maintaining skin elasticity in the dermis, and has collagen decomposition activity. When elastase is appropriately expressed and activated, it is involved in wound healing. However, when it is overexpressed or activated, elastin in the skin decomposes and the elasticity of the skin is lost. Therefore, the elastase inhibitor has a function of improving the wrinkles of the skin, and the uric acid and the like are used as the elastase inhibitor.

On the other hand, a composition for external application for improving skin wrinkles (Korean Patent No. 0507292), a composition for improving wrinkles containing natural extracts such as rhubarb, white mulberry and sandalwood (Korean Patent No. 1220903) Or a composition for external application for skin containing scleroglucan (Korean Patent Laid-Open Publication No. 2010-0043923), as well as studies on natural products such as a water-dispersible polymer in which a film-forming polymer composed of a polyurethane and an acrylic polymer is dispersed in water (Korean Registered Patent No. 1101363), which is a composition for external application for skin, which has been also studied. However, there has not yet been developed a composition for external application of skin for improving wrinkles derived from natural products satisfactory to consumers in terms of stability and skin wrinkle improvement effect.

Under these circumstances, the present inventors have made intensive efforts to develop an excellent composition for external application of skin for improving wrinkles by fermenting natural materials. As a result, it has been found that the extract of wheat germ fermented product and 2,6-dimethoxybenzoquinone (2,6-DMBQ: 2,6 -Dimethoxybenzoquinone) is superior in safety and has an excellent effect of improving collagen and elastin degradation while increasing collagen biosynthesis and improving skin wrinkles (for example, wrinkles in the eyes) when applied to skin.

The object of the present invention is to provide a cosmetic composition for prevention or improvement of skin wrinkles containing a compound of the following formula (1) or a fermented product of wheat germ or an extract thereof.

[Chemical Formula 1]

Another object of the present invention is to provide a pharmaceutical composition for preventing or treating skin wrinkles containing the compound of formula (I) or a fermented wheat germ or an extract thereof.

Another object of the present invention is to provide a quasi-drug composition for prevention or improvement of skin wrinkles containing the compound of formula (I) or a fermented product of wheat germ or an extract thereof.

Another object of the present invention is to provide a method for preventing, improving or treating skin wrinkles comprising the step of administering to a subject in need thereof a compound of formula 1, or a wheat germ fermented product or extract thereof, or a composition of the present invention .

In one aspect of the present invention, there is provided a cosmetic composition for preventing or improving skin wrinkles comprising a compound represented by the following formula (1) or a fermented wheat germ or an extract thereof.

The compound that can be included as an active ingredient in the cosmetic composition of the present invention can be represented by the following formula (1).

[Chemical Formula 1]

The compound represented by the formula (1) of the present invention is a compound named 2,6-dimethoxybenzoquinone (2,6-dimethoxybenzoquinone), which is chemically or biologically synthesized or commercially available Can be used. Or from natural products known to contain the compound of the present invention (for example, plants, etc.). However, the present invention is not particularly limited thereto. In the present application, it was confirmed that the compound represented by the formula (1) contained in the wheat germ fermented product or the extract had an effect of preventing or improving skin wrinkles.

As used herein, the term "wheat germ" means wheat germ. This is a nutrient-rich embryo of wheat kernel that is removed from the flour milling process, accounting for about 2 to 3% of the total wheat grain. Wheat germs are known to be rich in vitamin E (tocopherol), known to be antioxidant vitamins so far, and recent studies have shown that natural substances extracted from fermented wheat germs have the effect of restoring the damaged immune function of the human body. However, the effect of improving the wrinkles of wheat embryos is not known.

The wheat embryo herein may include, but is not limited to, the dried, ground, concentrated, and mixtures thereof of the wheat embryo.

As used herein, the term "fermentation" means any activity or process involving enzymatic or metabolic degradation of an organic material with a microorganism.

As used herein, the term "wheat germ fermentation product" refers to the result of enzymatic or metabolic degradation of wheat germ using microorganisms.

The wheat germ fermented product of the present invention may contain the compound of formula (1).

The wheat germ fermented product of the present invention may be obtained by inoculating a microorganism into a wheat embryo or a culture medium containing the same, followed by culturing. Specifically, the microorganism may be at least one selected from the group consisting of yeast, lactic acid bacteria, bacteria, and fungi.

The yeast may be, for example, Saccharomyces cerevisiae , S. ellipsoideus , S. coreanus , Saccharomyces cylindusensis (" Saccharomyces cerevisiae " S. carlsbergensis), Saccharomyces access to my Paz Astoria Augustine (S. pastorianus), Saccharomyces access to my lactis (S. lactis), Saccharomyces access to my ruksi (S. rouxii), to access Shijo Saccharomyces pombe Mai (Schizosaccharomyces pombe ), Zygosaccharomyces major , Hansenula anomala , Brettanomyces bruxellensis , B. custersianus , Dekkera , Dekkera anomala , Streptomyces olivochromogenes , or S. griseus may be used for the purpose of the present invention, Room or an improvement effect. For example, the yeast may be Saccharomyces cerevisiae.

The lactic acid bacteria may be, for example, Bifidobacterium sp.), Lactobacillus genus (Lactobacillus sp.), Lactococcus lactis in (Lactococcus sp.), Peddie Oh caucus in (Pediococcus sp.), Streptococcus genus (Streptococcus. sp), or the current Kono Stock in (Leuconostoc sp.), but it is not limited to those which can exhibit the effect of preventing or improving wrinkles of the skin for the purpose of the present invention. For example, the lactic acid bacteria is Bifidobacterium bipyridinium bushes (B. bifidum), Bifidobacterium breather probe (B. breve), Bifidobacterium ronggeom (B. longum), Bifidobacterium Annie Marlies (B. animalis), Bifidobacterium lactis (B. lactis), Lactobacillus ash's also a filler (L. acidophilus), Casey Lactobacillus (L. casei), Lactobacillus joined Lee (L. gasseri), Lactobacillus del Brewer L. delbrueckii spp., L. bulgaricus , L. helveticus , L. fermentum , L. paracasei , L. plantarum , L. reuteri , L. rhamnosus , L. salivarius , L. lactis , and the like), Lactobacillus spp ., Lactobacillus sp. , Peddie Oh Celebi jiae Caucus (P. cerevisiae), Peddie Oh Caucus kids CD Rock City (P. acidilactici), Streptococcus lactis (S. lactis), Streptococcus thermostat Phillies (S. thermophiles), Streptococcus Crescent Morris (S. cremoris), or the current mail center Stock Pocono Roy Rhodes (L. mesenteroides) Lt; / RTI > Lactic acid bacteria may be used herein in the same sense as lactic acid bacteria.

The fungus used in the fermentation may include, but is not limited to, mushrooms. Examples of the mushrooms include shiitake mushroom, oyster mushroom, mushroom mushroom, mushroom mushroom, mushroom mushroom, mushroom mushroom, Ginger mushroom, or mushroom, but it is not limited thereto as long as it can exhibit the effect of preventing or improving wrinkles of the skin for the purpose of the present invention.

The amount of inoculum, culture temperature, culture humidity, and incubation time of the microorganism used to produce the wheat germ fermented product of the present invention can be appropriately selected by those skilled in the art in consideration of the kind of microorganism used for fermentation. As a non-limiting example, the cultivation of the present invention can be carried out at a temperature of 20 ° C to 40 ° C for 12 to 60 hours. Specifically, the cultivation of the present invention is carried out at 25 ° C to 35 ° C, 28 ° C to 32 ° C or 30 ° C and / or 12 hours to 50 hours, 20 hours to 50 hours, 30 hours to 50 hours, Hour to 42 hours or 40 hours.

As used herein, the term "extract of wheat germ fermented product" refers to a substance from which microorganisms have been removed from a wheat germ fermentation product.

The removal of the present invention may include any method for removing microorganisms (for example, yeast cells) contained in microbial fermentations known in the art. Specifically, the extract of the wheat germ fermented product of the present invention may be a supernatant obtained by subjecting the wheat germ fermented product of the present invention to centrifugation. More specifically, the centrifugation may be carried out at a rotational speed of 6,000 rpm to 10,000 rpm, 7000 rpm to 9000 rpm, 7500 rpm to 8500 rpm, 7800 rpm to 8200 rpm or 8000 rpm and / 5 minutes to 40 minutes, 5 minutes to 30 minutes, 10 minutes to 120 minutes, 10 minutes to 90 minutes, 10 minutes to 60 minutes, 10 minutes to 40 minutes, 15 to 30 minutes, 15 to 120 minutes, 15 to 90 minutes, 15 to 60 minutes, 15 to 40 minutes, 15 to 30 minutes, 15 to 25 minutes, or 20 minutes.

The extract of the wheat germ fermented product of the present application may contain the compound of formula (1) of the present invention, though not particularly limited thereto.

The extract of the wheat germ fermented product of the present application includes the extract of the wheat germ fermented product of the present invention and an extract of all the formulations which can be formed using an extract such as a dilute solution, a concentrate, a dried product, a controlled preparation, a purified product or a mixture thereof. Specifically, the extract of the wheat germ fermented product of the present invention may be a dried product, more specifically, a lyophilized product.

In addition, the extract of the wheat germ fermentation product of the present invention can be obtained from the wheat germ fermentation product by any method as long as it has the effect of preventing, improving or treating wrinkles. As a non-limiting example, the wheat germ fermentation product is immersed in a solvent, A heating extraction method in which heating is carried out at 40 to 100 ° C, an ultrasonic extraction method in which ultrasonic waves are applied to the extraction, and a reflux extraction method using a reflux condenser. These methods may be performed alone or in combination of two or more methods.

The kind of the extraction solvent used in the extraction of the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent of the present invention include water, a C1-4 alcohol, hexane, ethyl acetate, chloroform, dichloromethane and mixtures thereof And the extraction solvent of the present invention may be hydrothermal.

The extract of the present invention may comprise fractions thereof. The term "fraction " as used herein refers to the result obtained by performing a fractionation to separate a specific component or a specific component group from a mixture containing various components.

The fractionation method for obtaining the fractions of the present invention is not particularly limited and may be carried out according to a method commonly used in the art. A solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing through an ultrafiltration membrane having a constant molecular weight cut-off value, various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity ), A combination thereof, and the like.

The kind of the fraction solvent used to obtain the fraction of the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvents of the present application include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of one or more.

The wheat germ fermented product or the extract thereof of the present invention may be used in an amount of 0.001 to 10% by weight based on the total weight of the composition of the present invention, specifically 0.01 to 7% by weight, 0.01 to 5% by weight, 0.01 0.05 to 10% by weight, 0.05 to 7% by weight, 0.05 to 5% by weight, 0.05 to 1% by weight, and 0.01 to 3% 0.1 wt.% To 7 wt.%, 0.1 wt.% To 5 wt.%, 0.1 wt.% To 3 wt.% %, 0.1% to 2%, 0.1% to 1%, 0.5% to 10%, 0.5% to 7%, 0.5% to 5%, 0.5% to 3% From 0.5% to 2%, from 0.5% to 1%, from 0.8% to 10%, from 0.8% to 7%, from 0.8% to 5%, from 0.8% to 3% %, 0.8 wt% to 2 wt%, 0.8 wt% may be included as to 1% or 1% by weight.

The wheat germ fermented product or extract thereof of the present invention may be contained in the composition of the present invention at 0.1 μg / ml to 200 μg / ml. Specifically, the wheat germ fermented product or extract thereof of the present invention may be added to the composition of the present invention at a concentration of 0.1 μg / ml to 150 μg / ml, 0.1 μg / ml to 100 μg / ml, 0.1 μg / ml to 70 μg / ml, Ml, 0.5 μg / ml to 200 μg / ml, 0.5 μg / ml to 150 μg / ml, 0.5 μg / ml to 100 μg / ml, 0.5 μg / ml to 70 μg / 0.8 μg / ml to 200 μg / ml, 0.8 μg / ml to 150 μg / ml, 0.8 μg / ml to 100 μg / ml, 0.8 μg / ml to 70 μg / ml and 0.8 μg / ml 1 to 50 μg / ml, 1 μg / ml to 200 μg / ml, 1 μg / ml to 150 μg / ml, 1 μg / ml to 100 μg / ml, 1 μg / ml to 70 μg / 5 to 50 μg / ml, 5 μg / ml to 200 μg / ml, 5 μg / ml to 150 μg / ml, 5 μg / ml to 100 μg / ml, 5 μg / ml to 70 μg / 8 μg / ml to 200 μg / ml, 8 μg / ml to 150 μg / ml, 8 μg / ml to 100 μg / ml, 8 μg / ml to 70 μg / 10 μg / ml to 200 μg / ml, 10 μg / ml to 150 μg / ml, 10 μg / ml to 1 00 microgram / ml, 10 microgram / ml to 70 micrograms / ml, or 10 micrograms / ml to 50 micrograms / ml.

The compound represented by the formula (1) may be used in an amount of 0.00001 wt% to 0.1 wt% based on the total weight of the composition, specifically 0.0001 wt% to 0.07 wt%, 0.0001 wt% to 0.05 wt%, 0.0001 wt% From 0.0001% to 0.03% by weight, from 0.0001% to 0.03% by weight, from 0.0001% by weight to 0.01% by weight, from 0.0005% by weight to 0.1% by weight, from 0.0005% by weight to 0.07% by weight, from 0.0005% by weight to 0.05% 0.001 wt% to 0.03 wt%, 0.001 wt% to 0.05 wt%, 0.001 wt% to 0.03 wt%, 0.0005 wt% to 0.02 wt%, 0.0005 wt% 0.005 wt% to 0.03 wt%, 0.005 wt% to 0.01 wt%, 0.005 wt% to 0.1 wt%, 0.005 wt% to 0.07 wt%, 0.005 wt% to 0.05 wt% 0.02 wt%, 0.005 wt% to 0.01 wt%, or 0.007 wt% It may be included in% by weight.

In addition, the compound represented by Formula 1 of the present invention may be contained in the composition of the present invention in an amount of 0.1 ng / ml to 1250 ng / ml. Specifically, the wheat germ fermented product or extract thereof of the present invention may be added to the composition of the present invention in an amount of 0.1 ng / ml to 1000 ng / ml, 0.1 ng / ml to 500 ng / ml, 0.1 ng / ml to 200 ng / ml, 1 ng / ml, 1 ng / ml to 90 ng / ml, 0.1 ng / ml to 60 ng / ml, 0.1 ng / ml to 30 ng / 1 ng / ml to 100 ng / ml, 1 ng / ml to 500 ng / ml, 1 ng / ml to 200 ng / ml, 1 ng / 1 ng / ml to 1000 ng / ml, 1 ng / ml to 500 ng / ml, 1 ng / ml to 1 ng / ml to 10 ng / ml, 1 ng / ml to 90 ng / ml, 1 ng / ml to 60 ng / ml, 1 ng / ml to 30 ng / ml, and 5 ng / ml 5 ng / ml to 500 ng / ml, 5 ng / ml to 200 ng / ml, 5 ng / ml to 120 ng / ml, 5 ng / ml 10 ng / ml to 10 ng / ml, 10 ng / ml to 10 ng / ml, and 10 ng / ml to 5 ng / ml to 60 ng / To 500 ng / ml, 10 ng / 10 ng / ml to 90 ng / ml, 10 ng / ml to 60 ng / ml, 10 ng / ml to 30 ng / ml, 15 ng / 15 ng / ml to 500 ng / ml, 15 ng / ml to 200 ng / ml, 15 ng / ml to 120 ng / ml, 15 ng / 30 ng / ml to 1250 ng / ml, 30 ng / ml to 1000 ng / ml, 30 ng / ml to 90 ng / ml, 15 ng / ml to 60 ng / 30 ng / ml to 60 ng / ml, 60 ng / ml to 500 ng / ml, 30 ng / ml to 200 ng / ml, 30 ng / ml to 120 ng / 60 ng / ml to 500 ng / ml, 60 ng / ml to 200 ng / ml, 60 ng / ml to 120 ng / ml or 60 ng / ml to 1000 ng / ml to 90 ng / ml.

As used herein, the term "wrinkles " refers to the scarring caused by degeneration of the skin, which can be caused by the cause of the gene, the reduction of collagen present in the skin dermis, and the external environment. The wrinkles may be meant to include skin aging or skin elasticity reduction. The skin aging refers to the type and intangible changes that appear on the skin as the age goes on. It refers to the effects of aging on the skin, such as stress, UV, smoking, medication, etc., as well as endogenous aging (natural aging) And exogenous aging that occurs as a cause of the disease. The photoaging included in the extrinsic aging means a phenomenon in which skin elasticity and moisture are reduced and wrinkles are formed when the sun ray is repeatedly exposed to the ultraviolet rays of the sunlight or the skin is damaged for a long time. Specifically, the photoaging may mean actinic elastosis, which causes denaturation or deposition of elastic fibers, heat insulation of collagen fibers, and the like.

The wrinkles of the present invention may be wrinkles occurring on the face, neck, and the like of the eyes, forehead, forehead, etc., and may specifically be wrinkles on the eyes.

According to one embodiment herein, the composition of the present invention can be used to promote procollagen biosynthesis, inhibit the expression of collagenase (MMP-1) by ultraviolet light, inhibit elastase activity and / or increase skin dermal density have.

As used herein, the term "prevention" means any action by which a composition according to the present invention inhibits or delays the occurrence of wrinkles.

As used herein, the term "improvement" means any action that at least reduces the degree of wrinkle-related parameters, e.g., wrinkles. Specifically, the improvement herein may be a decrease in the depth of the wrinkles, an increase in the density of the dermis, and / or a decrease in the number of wrinkles within a certain area.

The cosmetic composition of the present invention may be selected from the group consisting of solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, And the like.

The cosmetic composition of the present application may further comprise a cosmetically acceptable carrier.

The kind of the cosmetically acceptable carrier of the present invention is not particularly limited so long as it does not impair the activity and properties of the cosmetic composition of the present invention, and any cosmetically acceptable carrier conventionally used in the art can be used. Non-limiting examples of the cosmetically acceptable carrier include saline, sterilized water, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in combination of two or more. The cosmetically acceptable carriers herein may comprise non-naturally occuring carriers.

The cosmetically acceptable carriers herein vary according to the formulation of the cosmetic composition.

When the formulation of the cosmetic composition of the present invention is a paste, cream or gel, it is preferable to use an animal oil, a vegetable oil, a wax, a paraffin, a starch, a tracer, a cellulose derivative, polyethylene glycol, silicon, bentonite, silica, talc, zinc oxide May be used, but is not limited thereto.

When the formulation of the cosmetic composition of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder or the like may be used as a carrier component. But are not limited to, propellants such as hydrocarbons, propane / butane or dimethyl ether.

When the formulation of the cosmetic composition of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent may be used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, Propylene glycol, 1,3-butyl glycol oil and the like can be used. Particularly, it is possible to use an oil such as cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerol aliphatic ester, polyethylene glycol or sorbitan Fatty acid esters can be used, but are not limited thereto.

When the formulation of the cosmetic composition of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester , Microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tracant, but are not limited thereto.

When the formulation of the cosmetic composition of the present invention is a soap, it is preferable to use, as a carrier component, an alkali metal salt of a fatty acid, a fatty acid hemiester salt, a fatty acid protein hydrolizate, isethionate, a lanolin derivative, an aliphatic alcohol, a vegetable oil, But is not limited thereto.

In the case where the formulation of the cosmetic composition of the present invention is a pack, a fill-off pack containing polyvinyl alcohol or the like, a wash-off pack containing a pigment such as kaolin, talc, zinc oxide, , Or a mask sheet pack, and is not particularly limited thereto.

The cosmetic composition of the present invention may further comprise components included in conventional skin external agent components such as water, a surfactant, a moisturizer, a lower alcohol, a chelating agent, a bactericide, an antioxidant, an antiseptic, a pigment and a fragrance.

As another aspect for achieving the object of the present invention, the present invention provides a pharmaceutical composition for preventing or treating skin wrinkles comprising a compound of the following formula 1, or a fermented wheat germ or an extract thereof.

[Chemical Formula 1]

In the pharmaceutical composition of the present application, the compounds described above, the wheat germ, the fermented product of the wheat germ, the extract of the wheat germ fermented product, the skin wrinkle and the prevention are all described above.

As used herein, the term "treatment" means any action that causes the composition to improve or improve the symptoms of skin wrinkles. Specifically, it may be a decrease in the depth of the wrinkles, an increase in the density of the dermis, a decrease in the number of wrinkles in a certain area, and / or a wrinkle reduction.

In the present application, the pharmaceutical composition may further comprise a pharmaceutically acceptable carrier.

The term "pharmaceutically acceptable carrier" as used herein refers to a carrier or diluent that does not irritate the organism and does not interfere with the wrinkle prevention or therapeutic activity and properties of the pharmaceutical composition of the present invention. Examples of the pharmaceutical carrier which is acceptable for the composition to be formulated into a liquid solution include sterilization and sterilization which are suitable for a living body and include saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol And one or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added.

In addition, the pharmaceutically acceptable carriers herein may comprise non-natural carriers.

The pharmaceutical compositions herein may be administered in single or multiple doses in a pharmaceutically effective amount.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to prevent or treat a disease at a reasonable benefit / risk ratio applicable to medical prophylaxis or therapy, and the effective dose level will depend on the severity of the disease, , The body weight of the patient, the health, the sex, the sensitivity of the patient to the drug, the time of administration of the composition used, the route of administration and the rate of excretion, the duration of the treatment, factors including drugs used in combination with or co- May be determined by factors well known in the medical arts.

As used herein, the term "administering " means introducing a given substance into a subject in any suitable manner and may be administered via any conventional route by which the composition of the present invention can reach an in vivo target. The administration route of the composition of the present invention is not particularly limited, but may be orally or parenterally. Specifically, it can be administered parenterally, and more specifically, it can be applied to the skin (i.e., transdermal administration). Specifically, the administration of the present invention can be carried out once to four times a day, twice to three times, or twice. In addition, administration of the present invention can be carried out for more than 4 weeks, more than 8 weeks, 4 to 12 weeks or 8 to 12 weeks.

In another aspect of the present invention, there is provided a quasi-drug composition for preventing or improving skin wrinkles containing the compound of formula (1) or a fermented product of wheat germ or an extract thereof.

The compound of formula 1, the wheat germ, the wheat germ fermented product, the extract of the wheat germ fermented product, the skin wrinkle, the prevention and the improvement are all applied as described above in the quasi-drug composition of the present application.

As used herein, the term " quasi-drug "refers to products which are used for diagnosis, treatment, improvement, alleviation, treatment or prevention of diseases of human or animal, Quasi-drugs are products that are used for the purpose of treating or preventing diseases of humans or animals, products that are mild or have no direct action on the human body.

The quasi-drug composition of the present invention can be manufactured in a form selected from the group consisting of body cleanser, foam, soap, mask, ointment, cream, lotion, essence and spray, but is not limited thereto.

When the compound of Formula 1, the wheat germ fermented product, or the extract of the wheat germ fermented product is used as a quasi-drug additive, the extract of the compound of Formula 1, the wheat germ fermented product or the wheat germ fermented product may be directly added or the other quasi- And can be suitably used according to a conventional method.

In another aspect for achieving the object of the present invention, there is provided a method of treating skin wrinkles comprising administering to a subject in need thereof a compound of formula 1, a wheat germ fermented product or extract thereof, Prevention, amelioration, or treatment.

For the prevention, improvement or treatment of skin wrinkles of the present invention, the compound of formula 1, wheat germ, fermented product of wheat germ, extract of wheat germ fermented product, skin wrinkle, prevention, improvement, One bar applies.

The composition of the present invention is free from toxicity, promotes pro-collagen biosynthesis, inhibits the expression of collagenase and elastase by ultraviolet rays, and has effects of reducing dermal density and skin wrinkle depth, It can be used for therapeutic purposes.

FIG. 1 is a graph showing the results obtained by plotting a calibration curve using 2,6-DMBQ, which is a compound of formula 1 of the present invention, and then calculating the area of peaks using the calibration curve, This is the result of converting the DMBQ content.
FIG. 2 is a graph showing the results of performing a cytotoxicity test of an extract of wheat germ fermented product (CJ) according to an embodiment of the present invention on NHDF cells.
FIG. 3 shows the results of measurement of cytotoxicity of 2,6-DMBQ on human skin fibroblasts.
FIGS. 4A and 4B are graphs showing an extract of the wheat germ fermented product (FIG. 4A) and 2,6-DMBQ (FIG. 4B) according to one embodiment of the present invention in the form of type 1 procollagen biosynthesis.
5A and 5B are graphs comparing the inhibitory activity of MMP-1 production upon ultraviolet irradiation of the extract of wheat germ fermented product (FIG. 5A) and 2,6-DMBQ (FIG. 5B) according to one embodiment of the present invention.
FIG. 6 is a graph comparing the inhibition of elastase activity of an extract of a wheat germ fermentation product according to an embodiment of the present invention.
Fig. 7 is a view for explaining the wrinkle parameters R1 and R3 when eye wrinkles are measured. Fig.
FIGS. 8A to 8F are diagrams comparing an extract-containing product (CJD cream) of wheat germ fermented product according to one embodiment of the present invention and a negative control product (control cream). FIG. 8A is a graph showing the change in the wrinkles of the eye by time, FIG. 8B is a graph showing the increase / decrease of the wrinkles of the eye according to the use of the product at each point of time, and FIG. FIG. 8D is a graph showing changes in the density of skin dermis by time, FIG. 8E is a graph showing dendritic density increase / decrease rate according to use of a product by time, FIG. 8F is a graph showing changes in dermis density to be.
FIGS. 9A to 9F are views comparing an extract-containing product (CJD cream) of wheat germ fermented product according to an embodiment of the present invention and a positive control product (containing ADE cream: adenosine). FIG. 9A is a graph showing the change in the wrinkles of the eye at each time point, FIG. 9B is a graph showing the rate of increase and decrease of the wrinkles in the eye according to the use of the time, and FIG. FIG. 9D is a graph showing changes in densities of skin dermis at different points of time, FIG. 9E is a graph showing dendritic denseness increase / to be.

Hereinafter, the present invention will be described in more detail in the following examples. However, these examples are provided only for the understanding of the present application, and the present invention is not limited thereto.

Manufacturing example  One: Wheat embryo Fermented  Extract preparation

50 g of wheat embryo (CJ Cheiljedang) and 500 g of water were added to the flask, followed by thorough mixing and sterilization at 121 占 폚 for 15 minutes. Then, 5% (2.5 g) of dry yeast (Baker's yeast (Angelica japonica), Angel Yeast) was inoculated on the wheat germ, and fermented at 30 DEG C for 40 hours and then incubated at 8000 rpm for 20 minutes The supernatant was taken by centrifugation. The supernatant was lyophilized and recovered to prepare an extract of the wheat germ fermented product.

In this Example, the extract of the wheat germ fermented product was named 'CJ'.

Manufacturing example  2: Wheat embryo Fermented  Analysis of components of extract

The content of 2,6-dimethoxybenzoquinone (2,6-dimethoxybenzoquinone) was analyzed by high performance liquid chromatography (HPLC). The content of the extract was higher than that of wheat germ It was 700 ppm based on the lyophilized extract of the fermented product. The DMBQ content was determined by diluting commercially available 2,6-DMBQ (Sigma-Aldrich) by concentration using chloroform, then plotting the peak area by the peak area analyzed by HPLC, and then calculating the peak area of DMBQ in the extract of the wheat germ fermented product (Fig. 1).

In the following Experimental Examples and Examples, 2,6-DMBQ was purchased from Sigma-Aldrich.

Experimental Example 1 : Cell viability assay (cell viability assay)

The extract of wheat germ fermented product (CJ) of Preparation Example 1 was measured for cytotoxicity in NHDF cells. Specifically, NHDF cells were divided into 6 × 10 ³ cells / well in a 96-well plate and then cultured in FBM (Fibroblast Basal Medium) containing 0.1% insulin, 0.1% rhFGF, 0.1% gentamicin, Lonza, CC-3131) and incubated at 37 ° C for 24 hours in an incubator containing 5% carbon dioxide. After the incubation, the starvation state was maintained for 12 hours, and then the FBM medium (control) in which the extract (experiment) and the additive (supplement) of the wheat germ fermentation product of Production Example 1 were removed by concentration was added and cultured for 24 hours . Then, to measure the cell survival rate, WST-1 (water-soluble tetrazolium salt-1, Roche) was diluted 1/10 in FBM medium without additives and treated with 100 μl of each solution for 1 hour After the reaction, the absorbance at 450 nm was measured. Thereafter, relative cell viability in the case of treatment with the extract (CJ) of the wheat germ fermented product of Production Example 1 (experimental group) was expressed as a percentage with respect to the case where the NHDF cells were treated with the FBM except for the sample (control).

As a result, it was confirmed that no cytotoxicity was observed at a concentration of 200 μg / ml or less (FIG. 2). Therefore, in the subsequent in vitro experiments, the concentration of the sample was set at 50 μg / ml or less.

In addition, cytotoxicity of 2,6-DMBQ (Sigma-Aldrich) on human dermal fibroblast (HDF) was measured. Specifically, HDF cells were cultured in DMEM supplemented with 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin to a cell number of 6 × 10 ⁵ cells / well. The cells were cultured in a 5% CO ₂ incubator using a 100 mm cell culture dish, and the cells reaching confluence were subcultured using trypsin-EDTA. Then, HDF cells at a concentration of ² × 10 ³ cells / well were cultured in a 96-well cell culture plate for 24 hours in DMEM (Thermo) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin / streptomycin, 6-DMBQ. The 2,6-DMBQ treatment was performed by dissolving 2,6-DMBQ in water and diluting the stock in an amount of 1/2 by concentration. The resulting solution was added to DMEM (serum free, P / S 1%) medium to a final concentration of 0.3125 μg / ml, 0.625 μg / ml, and 1.25 μg / ml), and the cells were further cultured for 48 hours. After the incubation, the cells were replaced with DMEM medium containing 10% EZ-CYTOX (EZ-1000, Daeil lab service, Korea) and the absorbance was measured at 450 nm using a plate reader And cell viability was determined.

As a result, it was confirmed that no cytotoxicity was observed at a concentration of 1.25 μg / ml or less (FIG. 3).

Effect of DMBQ on the survival rate of HDF cells Concentration (μg / ml) Cell survival rate (%) Statistical analysis
(p-value) Average Standard Deviation Control (control) 100.0 2.5 - 0.3125 107.9 7.0 0.179 0.625 105.3 1.7 0.045 1.25 110.8 4.7 0.037

Experimental Example  2: evaluation of wrinkle-improving efficacy

2-1: Type 1 Procollagen  Biosynthesis promotion experiment

NHDF cells were plated in 48-well plates at 1 × 10 ⁴ cells / well and cultured in the same FBM medium as in Experimental Example 1 for 24 hours. Thereafter, the medium was removed, and the starvation state of the cells was maintained for 24 hours. Then, the wheat germ fermented product extract and 2,6-DMBQ of Production Example 1 were diluted in FBM (except for the additives) The cells were treated with 24, 24, and 30 ng / ml, 20 ng / ml, and 20 ng / ml of extracts: 1 μg / ml, 10 μg / ml and 50 μg / Time. The culture medium was then collected and the amount of procollagen was measured using a procollagen type I c-peptide (PIP) EIA kit (TAKARA, MK101). On the other hand, the cells attached to the bottom were washed with PBS, lysed with 1N NaOH, and the total amount of protein was measured to calculate the amount of procollagen synthesis per a certain protein.

As a result, it was confirmed that the extract of the wheat germ fermented product increased the amount of procollagen produced in a concentration-dependent manner (Fig. 4A). In addition, in the range of 15 ng / ml to 120 ng / ml for 2,6-DMBQ, the expression of procollagen was promoted to a statistically significant level. In the concentration range of 15 ng / ml to 30 ng / ml, (Table 2, Fig. 4b, Paired t-test: * p < 0.05, p <0.05) ** p < 0.01, *** p &lt; 0.001).

Concentration (ng / ml) The expression amount of type 1 procollagen (%) Statistical analysis
(p-value) Average Standard Deviation Control 100.0 11.6 - 15 172.4 2.6 0.0063 30 188.5 9.2 0.0006 60 177.8 5.3 0.0025 120 161.9 15.0 0.0057 TGF-β (5 ng / ml) 203.8 5.9 0.009

2-2: Collagenase ( MMP -1) expression inhibition experiment

The wrinkle-reducing effect of the sample was evaluated by measuring the expression level of collagenase (MMP-1, Matrix metalloproteinase-1) expressed by ultraviolet light in various wrinkle-forming mechanisms using an immuno-ELISA assay .

Specifically, NHDF cells were divided into 2x10 ⁴ cells / well on a 24-well plate and cultured in the same medium as Experimental Example 1 for 24 hours. After 24 hours, the medium was discarded and washed with DPBS, followed by addition of 200 μl of DPBS, and UV-B was irradiated at 40 mJ / cm 2. Then, the extracts (CJ) of the wheat germ fermented product of Preparation Example 1 at the same concentration as in Experimental Example 2-1 were each treated with the cells and cultured for 24 hours. Then, the amount of MMP-1 was measured with a human whole MMP-1 ELISA kit (R & D system, DY901), and the amount of MMP-1 measured was corrected to the total amount of protein.

In the case of the 2,6-DMBQ treatment, the amount of MMP-1 was measured by the same method except that the UV-B irradiation was performed at 15 mJ / cm ² in the above method, and retinoic acid was used as a positive control.

As a result, MMP-1 tended to decrease significantly in a concentration-dependent manner (FIG. 5A) as a result of treatment with the extract (CJ) of the wheat germ fermented product to the control (+) in which the expression of MMP-1 was increased by UVB irradiation.

In addition, the 2,6-DMBQ-treated group showed a significant MMP-1 inhibitory effect in the concentration range of 15 to 120 ng / ml, and the concentration-dependent pattern was observed at 120 ng / ml treatment 68% (Table 3, Fig. 5b).

Concentration (ng / ml) MMP-1 expression rate
(% of control) Statistical analysis
(p-value) Expression inhibition rate
(% of control Average Standard Deviation non-UV 61.8 6.0 - - The control (control) 100.0 10.3 - 0.0 15 92.5 16.6 0.5 19.7 30 89.5 14.8 0.4 27.4 60 83.2 9.8 0.1 44.1 120 73.7 6.6 0.0 68.7 Retinol acid
(200 ng / ml) 63.7 9.9 0.0 95.0

2-3: Elastase ( elastase ) Inhibition experiment

Inhibition of reaction between elastase and N-STANA (N-succinyl- (Ala) 3-p-nitroanilide) to confirm that the extract of wheat germ fermented product and 2,6-DMBQ inhibit the activity of elastase Was evaluated. First, 0.2M Tris-HCl (pH 8.0) containing 0.1% triton X-100 was added to NHDF cells of dermal fibroblast and homogenized through an ultrasonic grinder. The supernatant obtained by centrifugation at 3,000 rpm for 20 minutes was used as a sample for confirming elastase activity.

Each of the above samples (200 μg / ml, 0.2 M Tris-HCl buffer, and wheat germ fermented extract (CJ) of Preparation Example 1 was mixed at a concentration of 50 mM N-STANA at 37 ° C., Absorbance was measured. The degree of inhibition of elastase activity was then calculated relative to the negative control (denoted by "-") without the extract of the wheat germ fermented product. As a positive control, phosphoramidon (indicated as 10 mM, '+'), which is known as an elastase activity inhibitor, was used.

As a result, it was confirmed that the extract of wheat germ fermented product (50 μg / ml) showed an effect equivalent to that of the positive control while suppressing the elastase activity to about 62% of the negative control (FIG. 6).

Example 1: Preparation of Cosmetic Ingredients Containing Extracts of Wheat Germ Fermented Product

1-1 Manufacture of makeup creams

A cosmetic cream containing an extract of the wheat germ fermented product of Production Example 1 as an active ingredient was prepared according to a conventional method as in the composition (% by weight) shown in Table 4 below.

1-2: Wrinkle improvement of make-up cream Clinical assessment of efficacy

1-2-1: Outline of experiment

The wrinkle-improving effect of the makeup cream (hereinafter referred to as "CJD cream") prepared in Example 1-1 was evaluated in the negative control (cream containing purified water of the same amount in place of the extract of the wheat germ fermentation product in the composition of Table 4, (hereinafter referred to as "control cream") or a positive control (hereinafter referred to as "ADE cream", which is equivalent to 0.04% of adenosine as a raw material for improving wrinkle function, instead of extract of wheat germ fermentation product) Respectively. The subjects were 20 female Korean women aged between 30 and 55 who developed eye wrinkles (visual evaluation grade 3 or higher of Kyunghee University Skin Engineering Center SOP).

After randomization (block randomization), the control cream and ADE cream and CJD cream were applied to the area to be used for 12 weeks. After that, 0, 4, 8, 12, The effectiveness of the cream containing the extract of the wheat germ fermented product for improving the wrinkles of the human skin was evaluated by performing visual evaluation, instrument measurement (photographing, skin wrinkle, dermal density) and safety evaluation at the time point. Specific sample information and methods of use are summarized in Tables 5 and 6 below.

Clinical evaluation subjects were asked to wash their skin at each evaluation point, and after 20 minutes of skin stabilization in a space where air movement and direct sunlight were not observed under constant temperature and humidity conditions (22 ± 2 ° C, 50 ± 5%), . The measurement and evaluation procedures are summarized in Table 7 below.

Measurements of dermis were measured on the right and left cheeks of the clinical evaluators before the use (0 weeks), 4 weeks, 8 weeks, and 12 weeks after using the product, and the wrinkles of the right and left eyes were measured Respectively.

1-2-2: Control Cream Contrast Evaluation

Replica measurement

Skin-Visiometer® SV600 (Courage + Khazaka GmbH, Germany) is a device for measuring the degree of skin wrinkle improvement by analyzing the intensity of light emitted by light emitted from an artificial light source through a silicone material. And analyzed by Visiometer image analyzer software. The smaller the value of R1 and R3, the lower the wrinkle depth is to improve the skin wrinkles, and the unit is arbitrary unit (AU). As shown in FIG. 7, a roughness parameter (R-parameter) R1 represents a distance between a highest point and a lowest point of the profile due to skin roughness, and R3 represents an average roughness, Are equally divided into five lengths and then arithmetically averaged the R1 values in the respective regions.

As a result of the measurement, as shown in Table 8, the CJD cream was statistically significantly decreased at all times (4 weeks, 8 weeks, and 12 weeks) after the use of the product, compared with before use, and the wrinkle- It was excellent.

As a result of comparison between the groups, skin roughness (R 1) value and average roughness (R 3) value after 8 weeks of cream use were statistically significant in the CJD cream use group compared to the control cream use group, as shown in Table 9 and Figs. 8A to 8C Respectively.

Dermal density measurement

DermaScanC®USB is a high-resolution 20-MHz ultrasound imaging device that uses ultrasound to generate echoes of varying densities between different densities to image changes in the skin and changes in the dermis caused by collagen fiber reflectance. The size of the echo is synthesized by a computer and expressed in color to produce a two-dimensional image. In this study, dermis densities of the left and right cheeks of the subject were measured using the DermaScanC®USB at each evaluation point. The density values were analyzed in the photographed images.

Compared with before the cream was used, the intensity of the dermis was significantly increased (improved) at the end of 12 weeks of use of the product using the CJD cream (Table 10 and Figures 8d-8f).

In comparison between groups, CJD cream showed a statistically significant improvement (improvement) in the density of dermis after 12 weeks of use of the product (Table 11 and Figures 8d and 8f).

Safety evaluation

After 4 weeks, 8 weeks, and 12 weeks after the use of the test product (CJD cream and control cream), the skin condition of the subject of clinical evaluation was observed and the skin condition for subjective and objective stimulation was confirmed through question and answer with the subject And recorded and evaluated. As a result, no adverse skin reactions were observed in all clinical subjects (Table 12).

The results of the device evaluation were analyzed using SPSS® Package Program version 22. The uniformity of the measured values before use of the test product was tested using the Paired T-test before the use of the Sapiro-wilks test. Before and after the use of the product, the repeated measures ANOVA was used when the measured value satisfied the normal distribution, and the statistical analysis was performed using the non-parametric method (Krusckal-Wallis and Mann-Whitney U test) Respectively. Statistical significance was tested using the Repeated Measures ANOVA, taking into account the interdependence of the repeated measures in the same study subjects, and the significance level was set at p <0.05 . The questionnaire evaluation was analyzed using frequency analysis.

According to the results of the above clinical evaluation, it was not possible to observe the skin adverse reaction in all clinical evaluation subjects. CJD cream showed significant wrinkle improvement effect compared with the control cream.

1-2-3: Evaluation of ADE cream contrast

Replica measurement

The eye wrinkles were measured in the same manner as in 1-2-2. As a result, skin roughness (R 1) and average roughness (R 3) were significantly decreased (improved) at 8 weeks after using CJD cream (p <0.05) Table 13 and Figures 9a-9c). This improvement was superior to ADE cream.

The changes in the R-parameters at the time points between the groups are shown in Table 14 below. The wheat germ fermented extract is a natural extract, but the adenosine-containing ADE obtained through the chemical purification process (resin adsorption, ammonia, ethanol elution, etc.) Cream with the same level of effect.

Dermal density measurement

The dermal density was measured by the same method as 1-2-2. As a result, the CJD cream showed a statistically significant increase (improvement) in the intensity of dermal thickness at 8 weeks and 12 weeks after use (p <0.05) 15 and Figures 9d-9f). This improvement was similar to or higher than ADE cream.

As shown in Table 16, the wheat germ fermented extract had the same level of effect as ADE cream containing adenosine, which is a natural extract but has undergone a chemical refining process. I could.

Safety evaluation

After 4 weeks, 8 weeks, and 12 weeks after the use of the test product (CJD cream and ADE cream), the skin condition of the subject of clinical evaluation was observed and the skin condition for subjective and objective stimulation was confirmed through question and answer with the subject And recorded and evaluated. As a result, no skin adverse events were observed in all clinical evaluation subjects (Table 17).

According to the clinical evaluation results, the skin adverse reaction could not be observed in all clinical evaluation subjects, and the CJD cream showed a wrinkle improvement similar to the ADE cream.

From the foregoing, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the above-described examples are illustrative in all aspects and not restrictive. The scope of the present invention should be construed to cover all modifications and variations derived from the meaning and scope of the appended claims rather than the foregoing detailed description and equivalents thereof.

Claims (12)

A cosmetic composition for preventing or improving skin wrinkles comprising a compound of the following formula (1), or a wheat germ fermented product or an extract thereof.
[Chemical Formula 1]

The method according to claim 1,
The above-mentioned wheat germ fermented product or its extract contains the compound of formula (1).
The method according to claim 1,
Wherein the wheat germ fermented product is obtained by inoculating yeast into a wheat embryo or a culture medium containing the same and culturing the same.
The method of claim 3,
Wherein the yeast is Saccharomyces cerevisiae, wherein the cosmetic composition is for prevention or improvement of wrinkles of the skin.
The method of claim 3,
Wherein the culture is carried out at 20 캜 to 40 캜 for 12 hours to 60 hours.
The method according to claim 1,
Wherein the wheat germ fermented product or the extract thereof contains 0.001 wt% to 10 wt% of the total cosmetic composition.
The method according to claim 1,
Wherein the composition promotes pro-collagen biosynthesis.
The method according to claim 1,
Wherein the composition inhibits the expression of collagenase (MMP-1) by ultraviolet rays.
The method according to claim 1,
Wherein the composition inhibits elastase activity.
The method according to claim 1,
Wherein the composition increases the density of skin dermis.
A pharmaceutical composition for preventing or treating skin wrinkles comprising a compound of the following formula (1), or a wheat germ fermented product or an extract thereof.
[Chemical Formula 1]

A quasi-drug composition for prevention or improvement of skin wrinkles containing a compound of the following formula (1), or a fermented product of wheat germ or an extract thereof.
[Chemical Formula 1]

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